Embodiments of the invention relate to processes for preparing chiral azetidinones, such as 1-(4-fluorophenyl)-4(S)-(4-hydroxyphenyl)-azetidin-2-one, a compound useful as an intermediate in the preparation of hypocholesterolemic agents, and to the preparation of substituted carboxy and sulfonyloxy propionic acid esters, intermediates useful in the above mentioned process.
WO 95/08532 discloses a series of hypocholesterolemic agents comprising 3-hydroxypropyl azetidinones and describes several processes suitable for preparing these azetidinones. WO 93/02048 discloses a process to stereoselectively prepare 3- and 4-substituted azetidinones by cyclization of beta-amino amides. WO 95/08532 and WO 97/45406 disclose a method to prepare 3- and 4-substituted azetidinones by reacting 4-phenylbutyrolactones and 4-methoxybenzylideneaniline. WO 97/16424 discloses a method to prepare the desired 3- and 4-substituted azetidinones by reacting 4-fluorocinnamyl bromide and a lactam.
More recently U.S. Pat. No. 6,207,882 describes a process to generate 3- and 4-substituted azetidinones stereoselectively using p-fluorobenzoylbutyric acid and chiral 4-phenyloxazolidon-2-ones. U.S. Pat. No. 5,886,171 had also previously described a stereoselective process to the desired azetidinones starting from 3(S)-hydroxy-gamma-lactone. U.S. Pat. No. 6,133,001 describes an enzymatic microbial reduction of a 3-keto azetidinone. Other methods exist in the prior art which teach to process of converting the 3-unsubstituted azetidinone, which is the subject of this patent, into 3-, and 4-substituted azetidinone hypocholesterolemic agents, such as by the method described in U.S. Pat. No. 5,856,473.
Related processes may also be found in US Patent Application Publication Number 2004/0254369 A1, which corresponds to U.S. patent application Ser. No. 10/460,877. The references discussed within this application are hereby incorporated herein by reference.